Posts filed under ‘Infecciones virales’

Association Between CMV Reactivation and Clinical Outcomes in Immunocompetent Critically Ill Patients – Systematic Review and Meta-Analysis July 2018

Background

The aim of our systematic review was to investigate the association between cytomegalovirus (CMV) reactivation and outcomes in immunocompetent critically ill patients.

Methods

We searched electronic databases and gray literature for original studies and abstracts published between 1990 and October 2016. The review was limited to studies including critically ill immunocompetent patients. Cytomegalovirus reactivation was defined as positive polymerase chain reaction, pp65 antigenemia, or viral culture from blood or bronchoalveolar lavage. Selected patient-centered outcomes included mortality, duration of mechanical ventilation, need for renal replacement therapy (RRT), and nosocomial infections. Health resource utilization outcomes included intensive care unit and hospital lengths of stay.

Results

Twenty-two studies were included. In our primary analysis, CMV reactivation was associated with increased ICU mortality (odds ratio [OR], 2.55; 95% confidence interval [CI], 1.87–3.47), overall mortality (OR, 2.02; 95% CI, 1.60–2.56), duration of mechanical ventilation (mean difference 6.60 days; 95% CI, 3.09–10.12), nosocomial infections (OR, 3.20; 95% CI, 2.05–4.98), need for RRT (OR, 2.37; 95% CI, 1.31–4.31), and ICU length of stay (mean difference 8.18 days; 95% CI, 6.14–10.22). In addition, numerous sensitivity analyses were performed.

Conclusions

In this meta-analysis, CMV reactivation was associated with worse clinical outcomes and greater health resource utilization in critically ill patients. However, it remains unclear whether CMV reactivation plays a causal role or if it is a surrogate for more severe illness.

https://academic.oup.com/ofid/article/4/2/ofx029/2991368

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July 15, 2018 at 3:48 pm

Incidence, aetiology, and sequelae of viral meningitis in UK adults: a multicentre prospective observational cohort study

LANCET June 2018

Fundamento

La meningitis viral se reconoce cada vez más, pero se sabe poco acerca de la frecuencia con la que ocurre o las causas y los resultados en el Reino Unido. El objetivo fue determinar la incidencia, las causas y las secuelas en adultos del Reino Unido para mejorar el tratamiento de los pacientes y ayudar en la planificación de los servicios de salud.

Métodos

Realizaron un estudio de cohorte observacional prospectivo multicéntrico de adultos con sospecha de meningitis en 42 hospitales en toda Inglaterra. Anidado en este estudio, en la región noroeste del Servicio Nacional de Salud (NHS) (ahora parte de NHS England North), se realizó un estudio epidemiológico. Los pacientes eran elegibles si tenían 16 años o más, tenían meningitis clínicamente sospechada y se les realizó una punción lumbar o, si la punción lumbar estaba contraindicada, tenían sospecha clínica de meningitis y un patógeno apropiado identificado en el hemocultivo o en la PCR de sangre. Se excluyeron las personas con dispositivos ventriculares. Calculamos la incidencia de meningitis viral utilizando datos de pacientes de la región noroeste solo y usamos estos datos para estimar el número de casos estandarizados de población en el Reino Unido. Resultados de calidad de vida autoinformados y resultados neuropsicológicos de los pacientes, utilizando el EuroQol EQ-5D-3L, la Encuesta de salud de forma abreviada de 36 elementos (SF-36) y el cronograma de evaluación neuropsicológica de Aldenkamp y Baker, durante 1 año después de la admisión .

Recomendaciones

1126 pacientes se inscribieron entre el 30 de septiembre de 2011 y el 30 de septiembre de 2014. 638 (57%) pacientes tuvieron meningitis: 231 (36%) casos fueron virales, 99 (16%) fueron bacterianos y 267 (42%) tuvieron una causa desconocida 41 (6%) casos tuvieron otras causas. La incidencia anual estimada de meningitis viral fue de 2.73 por 100 000 y la de meningitis bacteriana fue de 1.24 por 100 000. La mediana de la estancia hospitalaria de los pacientes con meningitis viral fue de 4 días (IQR 3-7), aumentando a 9 días (6-12) en aquellos tratados con antivirales. La punción lumbar previa dio como resultado que se identificara más pacientes con una causa específica que aquellos que tuvieron una punción lumbar tardía. En comparación con la población del Reino Unido correspondiente a la edad, los pacientes con meningitis viral tuvieron una pérdida media de 0-2 años de vida ajustados por calidad (SD 0 · 04) en ese primer año.

Interpretación

Los virus son la causa más común de meningitis en adultos del Reino Unido y conducen a una morbilidad sustancial a largo plazo. Los retrasos en la punción lumbar y el tratamiento innecesario con antivirales se asociaron con estancias hospitalarias más prolongadas. Los diagnósticos rápidos y los tratamientos de racionalización pueden reducir la carga de la meningitis en los servicios de salud.

Fondos

Meningitis Research Foundation e Instituto Nacional de Investigaciones sobre la Salud del Reino Unido.

FULL TEXT

https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(18)30245-7/fulltext

PDF

https://www.thelancet.com/pdfs/journals/laninf/PIIS1473-3099(18)30245-7.pdf

July 6, 2018 at 8:21 am

Trends in the Molecular Epidemiology and Genetic Mechanisms of Transmitted HIV-1 Drug Resistance in a Large U.S. Clinic Population.

Clin Infect Dis. May 28, 2018

Rhee SY1, Clutter D1, Fessel WJ2, Klein D3, Slome S4, Pinsky BA5, Marcus JL6, Hurley L7, Silverberg MJ7, Kosakovsky Pond SL8, Shafer RW1.

Author information

1 Division of Infectious Diseases, Department of Medicine, Stanford University, Stanford, CA.

2 Department of Internal Medicine, Kaiser Permanente Northern California, San Francisco, CA.

3 Department of Infectious Diseases, Kaiser Permanente Northern California, San Leandro, CA.

4 Department of Infectious Diseases, Kaiser Permanente Northern California, Oakland, CA.

5 Department of Pathology, Stanford University, Stanford, CA.

6 Harvard Medical School and Harvard Pilgrim Health Care Institute, Oakland, CA.

7 Division of Research, Kaiser Permanente Northern California, Oakland, CA.

8 Department of Biology, Temple University, Philadelphia, PA.

Abstract

BACKGROUND:

There are few large studies of transmitted drug resistance (TDR) prevalence and the drug resistance mutations (DRMs) responsible for TDR in the U.S.

METHODS:

HIV-1 RT and protease sequences were obtained from 4,253 antiretroviral therapy (ART)-naïve individuals in a California clinic population from 2003-2016. Phylogenetic analyses were performed to study linkages between TDR strains and selection pressure on TDR-associated DRMs.

RESULTS:

From 2003-2016, there was a significant increase in overall (odds ratio [OR]=1.05 per year; 95% CI: 1.03 – 1.08; p<0.001) and nonnucleoside RT inhibitor (NNRTI)-associated TDR (OR=1.11 per year; 95% CI: 1.08 – 1.15; p<0.001). Between 2012 and 2016, TDR rates to any drug class ranged from 15.7%-19.2%, and class-specific rates ranged from 10.0%-12.8% for NNRTIs, 4.1%-8.1% for nucleoside RT inhibitors (NRTIs), and 3.6%-5.2% for protease inhibitors. K103N/S, Y181C, Y188L, and G190A mutations accounted for 88.5% of NNRTI-associated TDR. The thymidine analog mutations, M184V/I, and the tenofovir-associated DRMs K65R and K70E/Q/G/N/T accounted for 82.9%, 7.3%, and 1.4% of NRTI-associated TDR, respectively. The proportions of individuals with low-level resistance or higher to boosted atazanavir and darunavir were 2.2% and 0.3%, respectively. 37% of TDR strains clustered with other TDR strains sharing the same DRMs.

CONCLUSIONS:

Although TDR has increased significantly in this large cohort, many TDR strains are unlikely to influence the activity of currently preferred first-line ART regimens. The high proportion of DRMs associated with infrequently used regimens combined with the clustering of TDR strains suggest that some TDR strains are being transmitted between ART-naïve individuals.

FULL TEXT

https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciy453/5005024

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July 2, 2018 at 6:45 pm

Characterization of influenza virus variants induced by treatment with the endonuclease inhibitor baloxavir marboxil.

Sci Rep. June 25, 2018 V.8 N.1 P.9633.      doi: 10.1038/s41598-018-27890-4.

Omoto S1, Speranzini V2, Hashimoto T3, Noshi T3, Yamaguchi H3, Kawai M3, Kawaguchi K3, Uehara T3, Shishido T3, Naito A3, Cusack S4.

Author information

1 Shionogi & Co., Ltd., Osaka, Japan. shinya.oomoto@shionogi.co.jp

2 European Molecular Biology Laboratory, Grenoble Outstation, Grenoble, France.

3 Shionogi & Co., Ltd., Osaka, Japan.

4 European Molecular Biology Laboratory, Grenoble Outstation, Grenoble, France. cusack@embl.fr

Abstract

Baloxavir acid (BXA), derived from the prodrug baloxavir marboxil (BXM), potently and selectively inhibits the cap-dependent endonuclease within the polymerase PA subunit of influenza A and B viruses. In clinical trials, single doses of BXM profoundly decrease viral titers as well as alleviating influenza symptoms. Here, we characterize the impact on BXA susceptibility and replicative capacity of variant viruses detected in the post-treatment monitoring of the clinical studies. We find that the PA I38T substitution is a major pathway for reduced susceptibility to BXA, with 30- to 50-fold and 7-fold EC50 changes in A and B viruses, respectively.

The viruses harboring the I38T substitution show severely impaired replicative fitness in cells, and correspondingly reduced endonuclease activity in vitro. Co-crystal structures of wild-type and I38T influenza A and B endonucleases bound to BXA show that the mutation reduces van der Waals contacts with the inhibitor. A reduced affinity to the I38T mutant is supported by the lower stability of the BXA-bound endonuclease. These mechanistic insights provide markers for future surveillance of treated populations.

FULL TEXT

https://www.nature.com/articles/s41598-018-27890-4

PDF

https://www.nature.com/articles/s41598-018-27890-4.pdf

June 30, 2018 at 5:47 pm

Approved: Baloxavir marboxil

WHO Drug Information 2018 V.32 N.1 P.32

One-dose treatment for influenza

Product name: Xofluza®

Dosage form: Tablet

Class: cap-dependent endonuclease inhibitor

Approval: Ministry of Health, Labour and Welfare (MHLW) of Japan

Use: Treatment of influenza types A and B

Benefits: Treatment requires only a single oral dose regardless of age.

Shionogi & Co. Ltd Press

PDF

http://www.who.int/medicines/publications/druginformation/issues/WHO_DI_32-1.pdf

 

June 30, 2018 at 5:45 pm

Zika virus infection: epidemiology, clinical manifestations and diagnosis

Current Opinion in Infectious Diseases: October 2016 – Volume 29 – Issue 5 – p 459–466

Calvet, Guilherme Amaral; Santos, Flavia Barreto dos; Sequeira, Patricia Carvalho

Purpose of review

Zika virus (ZIKV) is an arbovirus previously believed to cause only a mild and self-limiting illness. Recently, it has emerged as a new public health threat that caused a large outbreak in French Polynesia in 2013–2014 and since 2015 an explosive outbreak in Brazil, with an increase in severe congenital malformations (microcephaly) and neurological complications, mainly Guillain–Barré syndrome (GBS). Since then, it has spread through the Americas. On 1 February 2016, the WHO declared the ZIKV epidemic in Brazil a Public Health Emergency of International Concern. We reviewed the epidemiology of ZIKV infection, clinical presentations and diagnosis. We highlighted the clinical features and nonvector borne transmission of the virus.

Recent findings

Association between ZIKV infection and severe foetal outcomes, including microcephaly and other birth defects; increased rate of GBS and other neurological complications due to the ongoing ZIKV outbreak; increased evidence to date of ZIKV being the only arbovirus linked to sexual transmission; the challenge of ZIKV diagnosis; and the need for a specific point-of care test in epidemic scenarios.

Summary

The findings illustrate the emergence of a viral disease with the identification of new associated disorders, new modes of transmission, including maternal–foetal and sexual transmission.

FULL TEXT

https://journals.lww.com/co-infectiousdiseases/Fulltext/2016/10000/Zika_virus_infection___epidemiology,_clinical.6.aspx?WT.mc_id=HPxADx20100319xMP

PDF (CLIC en ARTICLE as PDF)

June 30, 2018 at 10:51 am

Cancer Risk in Older Persons Living With Human Immunodeficiency Virus Infection in the United States

Clinical Infectious Diseases July 1, 2018 V.67 N.1 P.50–57

Parag Mahale; Eric A Engels; Anna E Coghill; Amy R Kahn; Meredith S Shiels

El riesgo de cáncer en 183.542 personas mayores que vivían con la infección por el virus de la inmunodeficiencia humana se evaluó utilizando datos del estudio de compatibilidad del cáncer de VIH/SIDA. El riesgo relativo de la mayoría de los cánceres disminuyó con la edad, pero los riesgos absolutos fueron más altos para algunos cánceres.

Background

Cancer risk is increased in persons living with human immunodeficiency virus (HIV) (PLWH). Improved survival has led to an aging of PLWH. We evaluated the cancer risk in older PLWH (age ≥50 years).

Methods

We included data from the HIV/AIDS Cancer Match Study (1996–2012) and evaluated risks of Kaposi sarcoma (KS), non-Hodgkin lymphoma (NHL), Hodgkin lymphoma, and cervical, anal, lung, liver, oral cavity/pharyngeal, breast, prostate, and colon cancers in older PLWH with risk in the general population by calculating standardized incidence ratios (SIRs) and excess absolute risks (EARs). Cancer risk by time since HIV diagnosis was estimated using Poisson regression.

Results

We identified 10371 cancers among 183542 older PLWH. Risk was significantly increased for KS (SIR, 103.34), NHL (3.05), Hodgkin lymphoma (7.61), and cervical (2.02), anal (14.00), lung (1.71), liver (2.91), and oral cavity/pharyngeal (1.66) cancers, and reduced for breast (0.61), prostate (0.47), and colon (0.63) cancers. SIRs declined with age for all cancers; however, EARs increased with age for anal, lung, liver, and oral cavity/pharyngeal cancers. Cancer risk was highest for most cancers within 5 years after HIV diagnosis; risk decreased with increasing time since HIV diagnosis for KS, NHL, lung cancer, and Hodgkin lymphoma.

Conclusions

Cancer risk is elevated among older PLWH. Although SIRs decrease with age, EARs are higher for some cancers, reflecting a greater absolute excess in cancer incidence among older PLWH. High risk in the first 5 years after HIV diagnosis for some cancers highlights the need for early HIV diagnosis and rapid treatment initiation.

abstract

https://academic.oup.com/cid/article/67/1/50/4793024

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June 28, 2018 at 9:09 am

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